Description du projet
Un hydrogel innovant servira de support pour aider dans la lutte contre les biofilms de Pseudomonas aeruginosa
Pseudomonas aeruginosa (P. aeruginosa) est une bactérie aérobie à Gram négatif commune dotée de mécanismes avancés de résistance multiple aux médicaments. Elle provoque des maladies chez les plantes, les animaux et les personnes, et est associée à des infections nosocomiales mortelles. P. aeruginosa forme des biofilms, qui constituent des communautés bactériennes structurées mille fois moins sensibles aux antibiotiques. Financé par le programme Actions Marie Skłodowska-Curie, le projet MONAGEL propose de combattre les biofilms de P. aeruginosa en développant un hydrogel composé de nanoparticules lipidiques réticulées équipées de principes actifs hydrophiles et hydrophobes encapsulés. L’applicabilité et l’efficacité de cette approche seront évaluées dans plusieurs lignées cellulaires et sa démonstration sera menée dans un modèle de coculture épithélium/biofilm comme preuve de concept en vue d’en poursuivre le développement.
Objectif
Pseudomonas aeruginosa (PA) is ubiquitous gram-negative bacteria. PA is a serious threat and is considered as a critical priority for treatment development by various institutions such as the World Health Organization. PA can cause infections on various location such as eyes, lung, skin (wounds). Immunocompromised patients are especially at risk, as PA is also able to colonize domestic and hospital fixtures. To add insult to injury, the infection is hard to treat and the number of antibiotic resistant PA is on the rise. The major challenge opposed by PA is its biofilm. Biofilms are a structured bacterial community embedded in a matrix composed of exopolysaccharides, proteins, extracellular DNA, and lipids. PA present in the biofilm are a thousand times less sensitive to antibiotics than their planktonic form. The MONAGEL project propose to fight the PA in the biofilm by developing a hydrogel made of cross-linked lipid nanoparticles. The lipophilic core of the lipid nanoparticles will be used to encapsulate hydrophobic active ingredients, the aqueous cavities of the gel will be used to encapsulate hydrophilic ones. The hydrophobic and hydrophilic compartment will enable work with a broad variety of molecules such as fluorescent probes (which will permit a thorough characterisation of the gel) or active ingredients such as antibiotics and pathoblockers. The latter molecule will be efficient to design the gel towards fighting PA biofilm either by inhibiting quorum sensing (bacterial communication) or lectin interaction (key role in biofilm formation). Well thought work and contingency plans have been put in place to ensure the success of MONAGEL development. The innocuity of the system will be assessed on various cell lines, and the antibiofilm efficacy will be tested on in vitro models. In the end, the MONAGEL efficacy will be demonstrated on a co-culture model (epithelium + biofilm) as a proof-of-concept to serve as a selling point for further development.
Champ scientifique
- natural sciencesbiological sciencesmicrobiologybacteriology
- natural sciencesbiological sciencesbiochemistrybiomoleculeslipids
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibiotics
- engineering and technologynanotechnologynano-materials
- medical and health sciencesbasic medicinepharmacology and pharmacydrug resistanceantibiotic resistance
Mots‑clés
Programme(s)
Régime de financement
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinateur
38124 Braunschweig
Allemagne